In order to assess the significance of activated oncogenes in the pathogenesis of human urinary tract tumors, fresh urothelial tumors were screened by DNA-mediated gene transfer (DNA transfection) using NIH/3T3 cells as recipients for the presence of such genes. Activation of HA-ras oncogene was found in 2 out of 23 specimens. By restriction endonuclease analysis, this activation was shown to be the result of somatic event. The basis for the activation was investigated through gene cloning and found to be due to a point mutation within 61st codon of its coding sequence in both cases. The frequency of Ha-ras activation by point mutation at 61st or 12th codon in human urothelial tumors was further estimated to be around 10% by both DNA transfection and restriction enzyme analysis. The involvement of other mechanisms of activation of oncogenes (gene amplification, gene rearrangement and others) are being explored. Modification of the effect of activated ras oncogenes in transformed cells will also be tried.